Thromboxane is released from blood vessel walls and causes coronary vasoconstriction, but there is evidence that thromboxane alone cannot explain coronary spasm in man. Since thromboxane is unstable, we used its stable mimic, U-46619 (Txm) to test whether Txm interacts with other vasoactive drugs or endogenous hormones. We gave graded doses of Txm, intracoronary (IC) to 10 anesthetized, open-chest pigs before and after the combination of arginine-8-vasopressin (AVP) and ergonovine (Erg), IC. Txm caused a dose-related increase in coronary vascular resistance (CVR = mean aortic pressure/mean coronary blood flow - m.Hg/ml/min), without changing heart rate or aortic pressure. AVP & Erg increassed CVR during the baseline bfore the second set of Txm doses: 3.29 + 1.27 to 4.06 + 1.20 mm.Hg/ml/min, (p Less than .05). The second set of Txm doses after AVP Erg showed greater relative and absolute increases in CVR than did the first set of Txm doses (P=.05). % Increase in CVR after Txm dose (ug) * mean+SD% Txm dose 0.1 0.5 1.0 Before *13+10% 23+21% 47+35% After AVP Erg 23+12% 43+13% 110+93% The effect of AVP+ Erg on the vasoconstrictor response to Txm was greater than their effect on the "control" CVR bfore Txm (p. Less than .01). Analysis of variance confirmed a true interaction rather than a simple additive effect of Txm and the combination of AVP and Erg (P. Less than .050). In conclusion, these data define a synergistic effect between Txm and AVP + Erg and illustrate the potential for a multifactorial etiology of coronary vasoconstriction. This type interaction may be relevant to other vasoconstrictors. The mechanism of this interaction is not known. It is unlikely that these results are explained mechanically by a similar strength of Txm-vasoconstrictor stimulis superimposed on a vascular bed already constricted by AVP + Erg because of the greater percent increase in CVR with Txm after AVP + Erg.